Nabumetone, 4-(6-methoxy-2-naphthyl)butan-2-one, is a known antiinflammatory drug. It has been synthesized and claimed at first in U.S. Pat. No. 4,061,779 granted on 1977. Other processes for the synthesis of nabumetone have subsequently been described and claimed. The synthesis of nabumetone by catalytic hydrogenation of 4-(6-methoxy-2-naphthyl)-4-hydroxybut-3-en-2-one obtained by condensation of 2-acetyl-6-methoxynaphthalene with ethyl acetate in presence of sodium hydride is described in U.S. Pat. No. 4,221,741 granted on 1980. The condensation reaction was carried out in anhydrous dimethylsulfoxide and under nitrogen. This condensation reaction, notwithstanding good yields, shows severe drawbacks, when used at industrial level, in terms of costs and of safety because of the use of remarkable amounts of sodium hydride and the consequent necessity of working in perfectly anhydrous and de-aerated ambient in order to avoid any risk of explosions.
The catalytic hydrogenation of compounds of formula 
wherein R and R1 are alkyl or alkylaryl groups, compounds obtained by condensation of 6-methoxy-2-naphthaldehyde with alkyl or alkylaryl acetoacetates, is described in U.S. Pat. Nos. 4,247,709 and 4,270,004 granted on 1981. Also this process is not advantageous from an economical point of view because of the high industrial cost of the 6-methoxy-2-naphthaldehyde. A great number of patent applications on alternative methods of synthesis of nabumetone and, among these, the published Dutch patent application NL 8700353, has subsequently been filed. In this patent application a process is described wherein 2-acetyl-5-bromo-6-methoxynaphthalene of formula 
is reacted with ethyl acetate in presence of an oily 80% dispersion of sodium hydride to give the sodium salt of the 4-(5-bromo-6-methoxy-2-naphthyl)-4-hydroxybut-3-en-2-one of formula 
that is reduced to 4-(6-methoxy-2-naphthyl)butan-2-one by means of a catalytic hydrogenation by using 10% palladium on carbon as catalyst in presence of an excess of sulfuric acid with respect to the amount necessary to free the 4-(5-bromo-6-methoxy-2-naphthyl)-4-hydroxybut-3-en-2-one, or its tautomer, from its sodium salt. Moreover, during the hydrogenation reaction hydrobromic acid forms which, if not neutralized, makes even more acidic the reaction ambient causing the formation of high amounts of reaction""s by-products and requiring costly acid-proof equipments. The poor selectivity of the reaction is made clear by the fact that the raw material coming from the hydrogenation has to be purified many times in order to obtain the necessary quality and the final yield is only 57%.
Present invention is a decisive improvement of the process described in the published Dutch patent application NL 8700353 for both reactions, the condensation and the hydrogenation reaction, used to get the nabumetone starting from the 2-acetyl-5-bromo-6-methoxynaphthalene intermediate. The condensation reaction described in the present invention is carried out in presence of an alkaline alcoholate, much less costly and more safe than sodium hydride used in NL 8700353. The reaction of hydrogenation is carried out, in the present inventon, not only in absence of sulfuric acid but even in presence of a basic substance in such an amount that most of the hydrobromic acid that comes from the hydrogenation reaction is neutralized so freeing from the reaction ambient the most of a reagent that, when present in remarkable amounts, is able to produce side-products which contaminate the desired product, make necessary a double purification and, finally, lower the end yield.
The hydrogenation reaction according to the invention described later can be carried out in standard equipments, gives a cleaner raw product from the reaction, which needs only one purification step, through crystallization or bisulphite complex, allowing the achievement of higher yields.
Summing up, the process described in NL 8700353 is a scarcely convenient process for the industrial manufacture of nabumetone, because of the high cost and unsafety of the reagent, the low yield and the need to make it in costly particular equipments. The process described in the present invention, constitues a remarkable improvement in the industrial manufacture of nabumetone also with reference to the already mentioned U.S. Pat. No. 4,221,741 because it uses the cheaper 4-(5-bromo-6-methoxy-2-naphthyl)-4-hydroxybut-3-en-2-one, or its tautomer, obtained from 2-acetyl-5-bromo-6-methoxynaphthalene that is an intermediate in the synthesis of the 2-acetyl-6-methoxynaphthalene described in our European patent EP 0440930 from which the 4-(-6-methoxy-2-naphthyl)-4-hydroxybut-3-en-2-one, or its tautomer, used in the abovementioned U.S. Pat. No. 4,221,741, is obtained. In fact, the reaction of acylation of 2-methoxynaphthalene carried out under normal conditions gives 1-acetyl-2-methoxynaphthalene instead of 2-acetyl-6-methoxynaphthalene. The reaction to get 2-acetyl-6-methoxynaphthalene has to be carried out in specified solvents very toxic and dangerous to handle like nitrobenzene, with which low yields are obtained, or liquid hydrofluoric acid or, as in the case of our European patent EP 0440930, position 1 has to be first protected by making 1 -bromo-2-methoxynaphthalene that by acylation under normal conditions gives 2-acetyl-5-bromo-6-methoxynaphthalene with yields higher than 90% from which, by dehalogenation, 2-acetyl-6-methoxynaphthalene is obtained.